The central nervous system (CNS) of vertebrates contains an enzyme complex which converts androgens to estrogens (aromatases). In brains of rats and rhesus macaques aromatase activity (AA) is distributed heterogeneously, is concentrated in areas that control reproductive behaviors and gonadotropin release, and in other brain regions from some unknown reason, e.g., in the amygdala. In many brains areas of the male rat, AA is androgen and androgen receptor dependent. Androgens stimulate AA by upregulating P450 AROM mRNA. The effects of androgens on AA and its P450 AROM mRNA in neural tissues of higher primates are not known. In this application the applicants propose experiments on nonhuman primates constructed around two Specific Aims (SA) which are based on prior work completed or ongoing in their laboratory. The first SA will use a recently developed Ribonuclease Protection Assay to measure P450 AROM MRNA in brains of rhesus macaques to study its distribution, hormonal regulation and relationship to AA in various brain parts and to compare these results with data already published in the rat. Rhesus monkeys develop a refractoriness to the negative feedback effects of steroid hormones after long-term castration (Cx). The second SA will study the effects of long-term Cx on AA, and androgen receptor (AR) dynamics and their respective RNAs in the monkey brain in order to understand the cellular components of this refractory state. Since estrogens have a wide range of neurotropic effects, in situ estrogen formation by the brain associated with sex steroid refractory states may explain some neurodeficiencies found in aging and certain diseased states discussed in the application. These experiments, when completed, should provide important new information for understanding the role of in situ estrogen formation, its distribution and control in nonhuman primate brains. This information can be used as a model to form hypotheses about the role of estrogens in human brain function.